Multiple global change drivers are increasing the present and future novelty of environments and ecological communities. However, most assessments of environmental novelty have focused only on future climate and were conducted at scales too broad to be useful for land management or conservation. Here, using historical county-level datasets of agricultural land use, forest composition, and climate, we conduct a regional-scale assessment of environmental novelty for Wisconsin landscapes from ca. 1890 to 2012. Agricultural land-use data include six cropland types, livestock densities for four livestock species, and human populations. Forestry data comprise biomass-weighted relative abundances for 15 tree genera. Climate data comprise seasonal means for temperature and precipitation. We found that forestry and land use are the strongest cause of environmental novelty (NoveltyForest=3.66, NoveltyAg.=2.83, NoveltyClimate=1.60, with Wisconsin’s forests transformed by early 20th-century logging and its legacies and multiple waves of agricultural innovation and obsolescence. Climate change is the smallest contributor to contemporary novelty, with precipitation signals stronger than temperature. Magnitudes and causes of environmental novelty are strongly spatially patterned, with novelty in southern Wisconsin roughly twice that in northern Wisconsin. Forestry is the most important cause of novelty in the north, land use and climate change are jointly important in the southwestern Wisconsin, and land use and forest composition are most important in central and eastern Wisconsin. Areas of high regional novelty tend also to be areas of high local change, but local change has not pushed all counties beyond regional baselines. Seven counties serve as the best historical analogues for over half of contemporary Wisconsin counties (40/72), and so can offer useful historical counterparts for contemporary systems and help managers coordinate to tackle similar environmental challenges. Multi-dimensional environmental novelty analyses, like those presented here, can help identify the best historical analogues for contemporary ecosystems, places where new management rules and practices may be needed because novelty is already high, and the main causes of novelty. Separating regional novelty clearly from local change and measuring both across many dimensions and at multiple scales thus helps advance ecology and sustainability science alike.